The alcohol intake of human and animal mothers affects the brain development of the offspring. One basic mechanism is that ethanol reduces the number of neurons in various brain regions, such as cerebral cortices, hippocampi, cerebella and olfactory muscles. The reaction of ethanol leads to altered neuronal migration and increased cell death. Exposure to ethanol during brain development can provoke neurodevelopmental defects referred to as fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS), depending on their severity, with an array of neurological disorders including hyperactivity, learning and memory deficits, mental retardation, psychosis, depression, and schizophrenia.
Ethanol causes craniofacial anomaly by apoptosis and neurodegeneration within 12 hours after exposure. Such neurodegeneration occurs because ethanol has NMDA antagonist and GABA mimetic properties and is responsible for the abnormal inhibition of neuronal activity, such as apoptosis induction.
Fetal alcohol spectrum disorders (FASD) appear in one of 100 children in USA, and it is known that many mechanisms, including oxidative stress, induction of apoptosis, excitotoxicity, destruction of cell-cell interaction, and inhibition of growth factor activity, contribute to neurotoxicity. Ethanol damages the developing brain by affecting neurogenesis, neuronal migration, or cell survival. This shows that FAS is the major non-genetic cause of mental retardation. Despite this increase in awareness of FAS, alcohol intake and excessive drinking during pregnancy have increased in recent years, and currently there are no effective treatments to prevent or revert FAS in the fetus in the mother.
The injury of free radicals and the rapid change in intracellular Ca2+ are estimated to be elements of signaling pathways activated by ethanol exposure. During the brain growth spurt period in which the brain develops into a multicellular organism, neurons are sensitive to alcohol exposure. The human growth spurt spans the last trimester of pregnancy to several years after birth, but the rodent growth spurt occurs after birth. Thus, studies on alcohol exposure in developed animal models such as rodents are excellent means for investigating the mechanism about the effect of ethanol on human brain development.
Meanwhile, plant-derived osmotin is involved in regulation of fatty acid oxidation, glucose uptake, phosphorylation (AMP kinase) and signal transduction pathways. It is known that osmotin (24 kDa) is a stable protein belonging to the PR-5 family having homology with sweet-tasting protein thaumatin and induces intracellular signaling in yeasts. Osmotin is resistant to heat, acidity and enzymes, and can circulate through the body without being broken down by digestion. Such osmotin is homologous to adiponectin present in animals, and adiponectin appears to have anti-inflammatory, anti-diabetic and anti-atherogenic activities. However, osmotin has been studied mainly on its effects on obesity or diabetes, and other effects are not found.
Under these circumstances, the present inventors have made extensive efforts to investigate the effects of osmotin on neurodegenerative diseases and other neurological diseases, and as a result, have found that osmotin has the effect of inhibiting the induction of neuronal apoptosis to prevent and treat fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS), which are accompanied by neurological disorders, learning and memory deficits, mental retardation, psychosis, depression, and schizophrenia, thereby completing the present invention.